Introduction
Polymer coatings enhance the capabilities of many of today's medical devices. Some coatings add such properties as lubricity, biocompatibility, and anti-microbial properties to device surfaces. Other coatings can be used to deliver therapeutic compounds from devices, or make implanted devices more easily detected by imaging systems.
For coatings designed to deliver therapeutic compounds, the compounds are usually coated on to the surface of the polymer coating. To be embedded in the polymer itself, which would lend more control to therapeutic compound release, the compound is incorporated during the polymerization reaction. However, most polymerization reaction conditions are incompatible with the therapeutic compounds maintaining their pharmacological attributes. Especially damaging reaction conditions include heat and γ irradiation.
Coating a device, such as a medical device (e.g., a stent), uses processes where a polymer is dissolved in a solvent, such as ethanol. The device is coated with the polymer using an appropriate method, such as dipping the device into the polymer solution or by spraying the polymer solution onto the device. Upon coating, the device is usually subjected to a curing condition, such as heat and γ irradiation. A drug can be loaded onto the coating by dipping or spraying techniques after the heat and γ irradiation steps, but results in the drug remaining primarily on the surface of the polymer.
For examples of conventional heat or γ irradiation cures, see (Bowers et al., 1997; Bowers et al, 2000; Bowers et al., 2001; Bowers et al., 1998). The BiodivYsio™ stent (product of Biocompatibles UK Ltd, Farnham, Surrey; UK) is coated with a biocompatible phosphorylcholine (PC) polymer comprised of 2-methacryloyloxyethyl phosphorylcholine, lauryl methacrylate, 2-hydroxypropyl methacrylate and 3-trimethoxysilylpropyl methacrylate monomers. The coating, once applied, is cured with heat, typically 70° C. for a minimum of 4 hours, and γ irradiated to insure proper material characteristics, such as cross-link density. These conditions, however, severely restrict the uses of the polymer coating to contain sensitive materials. Examples of some sensitive materials (other than therapeutic compounds) include nylon 11 that cannot tolerate high temperatures before undergoing a glass transition (between 45-48° C.); and polytetrafluoroethylene, which suffers deterioration of its mechanical properties when exposed to γ irradiation. These materials are used in the construction of some embolic filter devices. In addition, the efficacy of drug that is loaded within the PC polymer matrix for controlled local delivery is often compromised by excessive processing conditions. Such cures are also taught throughout the literature. For example, Lewis et al. (2001) describe preparation and characterization of phosphorylcholine (PC) polymers that includes the use of heat and γ irradiation to cross-link trimethoxysilyl groups of 3-trimethoxysilylpropyl methacrylate monomers (a pendant group extending from the backbone of a PC polymer) (Lewis et al., 2001). The synthesis and characterization for copolymers of 2-methacryloyloxyethylphosphorylcholine (MPC) and lauryl methacrylate (LMA), which do not contain 3-trimethoxysilylpropyl methacrylate monomer and therefore cannot undergo cross-linking through trimethoxysilyl groups has also been described (Lewis et al., 2000).
Other methacrylate copolymers incorporating the 3-trimethoxysilylpropyl methacrylate monomer for curable coating systems have been used in other industries, such as the automotive industry for automotive refinishing (automotive topcoats) where a final clear coating is applied over a pigmented basecoat. These systems, however, typically require the addition of a catalyst (such as tetrabutyltitanate or dibutyltin dilaurate), as well as excessive heat for an extended period of time to provide proper cure—all of which can restrict the incorporation of suitable therapeutic compounds to those that are not degraded or otherwise adversely affected (e.g., loss of therapeutic activity) by the curing steps.
Finally, a moisture curable sealant composition where alkoxysilane functionality can be grafted onto an acrylic polymer backbone to produce an alkoxysilane-functionalized acrylic polymer which can then be reacted with a reactive silanol solution containing reactive silicone (and, optionally, a silane cross-linker) to form a silicone-acrylic hydride polymer network through a silanol-alkoxysilane condensation reaction has been described (Hernandez, 1994). The resulting cross-linked silicone-acrylic hybrid polymer can be used in sealant, adhesive or coating compositions.